This is a proposal to establish a new Center for Computational Biology (CCB). Our goals are to apply computational and mathematical approaches to the study of genes, cells, systems and whole brain. The major objectives of the CCB are to develop, implement and test computational biology strategies that are applicable across spatial scales and biological systems. This will help elucidate characteristics and relationships that would otherwise be impossible to detect and measure. Interactions fostered by this multidisciplinary program will result in novel strategies to fundamental problems that can be applied to genetics, biochemistry, molecular biology and brain mapping. Our view of computational biology considers the problem of constructing atlases - sets of maps on different spheres of biological information that span many scales and modalities from genotype to phenotype. In this proposal we introduce the concept of a computational arias as a database-like infrastructure that rests on mathematical advances in modeling and optimization. We will develop the infrastructure for such a computational atlas resulting in a platform for addressing large-scale modeling problems that before now have been intractable. There are 4 driving biological projects in Core 3 of this proposal: (1) Mapping Language Development Longitudinally, (2) Mapping Brain Changes in Alzheimer's & Those at Risk, (3) Mechanisms Underlying the Clinical Progression of MS and EAE, and (4) Genetic Influences on Brain Structure in Schizophrenia. Each includes essential elements of computational biology: modeling, imaging, bioinformatics, biocomputing and data management. Each was chosen specifically because of its symbiotic relationship to Cores 1 and 2 where computational science and computational tools will be developed. The entire project is integrated. The Cores not only provide support for the development of research projects but also for programmatic development. The Infrastructure and Resources Core will provide hardware, software, visualization and database contributions to facilitate sharing and cooperative development. The Education and Training Core will nourish this program by integrating training opportunities and encouraging students to enter this important area. The Dissemination Core will ensure that the products of our efforts will be communicated to the outside world efficiently and broadly. The Administrative and Management Core will provide oversight, documentation, leadership and communication.